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Blood, 1 June 2006, Vol. 107, No. 11, pp. 4540-4548. Prepublished online as a Blood First Edition Paper on February 23, 2006; DOI 10.1182/blood-2005-10-4042. This Article Full Text Full Text (PDF) All Versions of this Article: 2005-10-4042v1 107/11/4540    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Fu, L. Articles by Ford, R. J. Search for Related Content PubMed PubMed Citation Articles by Fu, L. Articles by Ford, R. J. Related Collections Neoplasia Apoptosis Signal Transduction Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA Constitutive NF-B and NFAT activation leads to stimulation of the BLyS survival pathway in aggressive B-cell lymphomas Lingchen Fu, Yen-Chiu Lin-Lee, Lan V. Pham, Archito Tamayo, Linda Yoshimura, and Richard J. Ford From the Department of Hematopathology, the University of Texas M. D. Anderson Cancer Center, Houston, TX, and the University of Texas Graduate School of Biomedical Sciences at Houston, TX. B-lymphocyte stimulator (BLyS), a relatively recently recognized member of the tumor necrosis factor ligand family (TNF), is a potent cell-survival factor expressed in many hematopoietic cells. BLyS binds to 3 TNF-R receptors, TACI, BCMA, BAFF-R, to regulate B-cell survival, differentiation, and proliferation. The mechanisms involved in BLYS gene expression and regulation are still incompletely understood. In this study, we examined BLYS gene expression, function, and regulation in B-cell non-Hodgkin lymphoma (NHL-B) cells. Our studies indicate that BLyS is constitutively expressed in aggressive NHL-B cells, including large B-cell lymphoma (LBCL) and mantle cell lymphoma (MCL), playing an important role in the survival and proliferation of malignant B cells. We found that 2 important transcription factors, NF-B and NFAT, are involved in regulating BLyS expression through at least one NF-B and 2 NFAT binding sites in the BLYS promoter. We also provide evidence suggesting that the constitutive activation of NF-B and BLyS in NHL-B cells forms a positive feedback loop associated with lymphoma cell survival and proliferation. Our findings indicate that constitutive NF-B and NFAT activations are crucial transcriptional regulators of the BLyS survival pathway in malignant B cells that could be therapeutic targets in aggressive NHL-B. 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